Thyroid-clock interaction in liver metabolism

Lübeck researchers decipher the interaction of the thyroid gland and time of day in the control of liver metabolism.

The thyroid hormones, triiodothyronine (T3) and thyroxin (T4), are important regulators of energy metabolism which also is subject to marked variations across the day. Such 24-hour rhythms in physiology and behavior are controlled by an internal, so-called circadian clock system present in all cells of the body.

Lübeck researchers from the Lübeck Institute of Neurobiology together with colleagues from the Institute of Endocrinology & Diabetes, Kiel, Stockholm, and Brisbane used a mouse model of thyroid hormone supplementation to study liver clock-thyroid hormone interaction in the regulation of metabolic rhythms. They found that, despite predicting metabolic turnover on the long run, thyroid hormones do not act as circadian markers of metabolic output. However, high thyroid hormone levels profoundly alter molecular liver rhythms downstream of the liver circadian clock itself with time-of-day specific effects on major metabolic outputs.

These data suggest that time-of-day critically affects thyroid hormone action in the liver. Therefore, the treatment of thyroid disorders may benefit from considering time as a regulatory factor. Clinical studies on the rhythmic regulation of thyroid hormone action are needed to further develop this approach.

de Assis LVM, Harder L, Lacerda JT, Parsons R, Kaehler M, Cascorbi I, Nagel I, Rawashdeh O, Mittag J, Oster H (2022) Rewiring of liver diurnal transcriptome rhythms by triiodothyronine (T3) supplementation. Elife 11. DOI: 10.7554/eLife.79405

This work was funded by the DFG as part of the LocotTact Collaborative Research Centre (CRC/TR 296).